ID   IDHC_PONAB              Reviewed;         414 AA.
AC   Q5R9C5; Q5RET8;
DT   30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2006, sequence version 2.
DT   24-JAN-2024, entry version 115.
DE   RecName: Full=Isocitrate dehydrogenase [NADP] cytoplasmic;
DE            Short=IDH;
DE            Short=IDH1;
DE            EC=1.1.1.42 {ECO:0000250|UniProtKB:O88844};
DE   AltName: Full=Cytosolic NADP-isocitrate dehydrogenase;
DE   AltName: Full=IDPc;
DE   AltName: Full=NADP(+)-specific ICDH;
DE   AltName: Full=Oxalosuccinate decarboxylase;
GN   Name=IDH1;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Catalyzes the NADP(+)-dependent oxidative decarboxylation of
CC       isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate),
CC       which is required by other enzymes such as the phytanoyl-CoA
CC       dioxygenase (By similarity). Plays a critical role in the generation of
CC       NADPH, an important cofactor in many biosynthesis pathways (By
CC       similarity). May act as a corneal epithelial crystallin and may be
CC       involved in maintaining corneal epithelial transparency (By
CC       similarity). {ECO:0000250|UniProtKB:O75874,
CC       ECO:0000250|UniProtKB:Q9XSG3}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH;
CC         Xref=Rhea:RHEA:19629, ChEBI:CHEBI:15562, ChEBI:CHEBI:16526,
CC         ChEBI:CHEBI:16810, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.42;
CC         Evidence={ECO:0000250|UniProtKB:O88844};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19630;
CC         Evidence={ECO:0000250|UniProtKB:O88844};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:O88844};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000250|UniProtKB:O88844};
CC       Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit.
CC       {ECO:0000250|UniProtKB:O88844};
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:O88844}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:P41562}.
CC   -!- PTM: Acetylation at Lys-374 dramatically reduces catalytic activity.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC       dehydrogenases family. {ECO:0000305}.
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DR   EMBL; CR857428; CAH89719.1; -; mRNA.
DR   EMBL; CR859464; CAH91635.1; -; mRNA.
DR   RefSeq; NP_001124781.1; NM_001131309.1.
DR   RefSeq; XP_009236322.1; XM_009238047.1.
DR   RefSeq; XP_009236323.1; XM_009238048.1.
DR   RefSeq; XP_009236324.1; XM_009238049.1.
DR   AlphaFoldDB; Q5R9C5; -.
DR   SMR; Q5R9C5; -.
DR   STRING; 9601.ENSPPYP00000014668; -.
DR   Ensembl; ENSPPYT00000015262.3; ENSPPYP00000014668.2; ENSPPYG00000013125.3.
DR   GeneID; 100171634; -.
DR   KEGG; pon:100171634; -.
DR   CTD; 3417; -.
DR   eggNOG; KOG1526; Eukaryota.
DR   GeneTree; ENSGT00390000012547; -.
DR   HOGENOM; CLU_023296_1_1_1; -.
DR   InParanoid; Q5R9C5; -.
DR   OMA; HGTVQRH; -.
DR   OrthoDB; 423at2759; -.
DR   TreeFam; TF300428; -.
DR   Proteomes; UP000001595; Chromosome 2B.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR   GO; GO:0005777; C:peroxisome; IEA:Ensembl.
DR   GO; GO:0004450; F:isocitrate dehydrogenase (NADP+) activity; ISS:UniProtKB.
DR   GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR   GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR   GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR   GO; GO:0006103; P:2-oxoglutarate metabolic process; ISS:UniProtKB.
DR   GO; GO:0006749; P:glutathione metabolic process; IEA:Ensembl.
DR   GO; GO:0006097; P:glyoxylate cycle; IEA:UniProtKB-KW.
DR   GO; GO:0006102; P:isocitrate metabolic process; ISS:UniProtKB.
DR   GO; GO:0071071; P:regulation of phospholipid biosynthetic process; IEA:Ensembl.
DR   GO; GO:0060696; P:regulation of phospholipid catabolic process; IEA:Ensembl.
DR   GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.718.10; Isopropylmalate Dehydrogenase; 1.
DR   InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR   InterPro; IPR004790; Isocitrate_DH_NADP.
DR   InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR   NCBIfam; TIGR00127; nadp_idh_euk; 1.
DR   PANTHER; PTHR11822:SF28; ISOCITRATE DEHYDROGENASE [NADP] CYTOPLASMIC; 1.
DR   PANTHER; PTHR11822; NADP-SPECIFIC ISOCITRATE DEHYDROGENASE; 1.
DR   Pfam; PF00180; Iso_dh; 1.
DR   PIRSF; PIRSF000108; IDH_NADP; 1.
DR   SMART; SM01329; Iso_dh; 1.
DR   SUPFAM; SSF53659; Isocitrate/Isopropylmalate dehydrogenase-like; 1.
DR   PROSITE; PS00470; IDH_IMDH; 1.
PE   2: Evidence at transcript level;
KW   Acetylation; Cytoplasm; Glyoxylate bypass; Magnesium; Manganese;
KW   Metal-binding; NADP; Oxidoreductase; Phosphoprotein; Reference proteome;
KW   Tricarboxylic acid cycle.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   CHAIN           2..414
FT                   /note="Isocitrate dehydrogenase [NADP] cytoplasmic"
FT                   /id="PRO_0000236187"
FT   BINDING         75..77
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         77
FT                   /ligand="substrate"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         82
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         94..100
FT                   /ligand="substrate"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         109
FT                   /ligand="substrate"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         132
FT                   /ligand="substrate"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         212
FT                   /ligand="substrate"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /evidence="ECO:0000250|UniProtKB:O88844"
FT   BINDING         252
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         260
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         275
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         279
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         310..315
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   BINDING         328
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   SITE            139
FT                   /note="Critical for catalysis"
FT                   /evidence="ECO:0000250"
FT   SITE            212
FT                   /note="Critical for catalysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   MOD_RES         42
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   MOD_RES         81
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O88844"
FT   MOD_RES         126
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O88844"
FT   MOD_RES         224
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O88844"
FT   MOD_RES         233
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O88844"
FT   MOD_RES         243
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O88844"
FT   MOD_RES         321
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O75874"
FT   MOD_RES         389
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O88844"
FT   MOD_RES         400
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O88844"
FT   CONFLICT        25
FT                   /note="L -> Q (in Ref. 1; CAH89719)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        226
FT                   /note="I -> T (in Ref. 1; CAH91635)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        331
FT                   /note="A -> V (in Ref. 1; CAH91635)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        411
FT                   /note="Q -> L (in Ref. 1; CAH89719)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   414 AA;  46699 MW;  73CB3A9AC5E411BA CRC64;
     MSKKISGGSV VEMQGDEMTR IIWELIKEKL IFPYVELDLH SYDLGIENRD ATNDQVTKDA
     AEAIKKYNVG VKCATITPDE KRVEEFKLKQ MWKSPNGTIR NILGGTVFRE AIICKNIPRL
     VSGWVKPIII GRHAYGDQYR ATDFVVPGPG KVEITYTPSD GTQKVTYLVH NFEEGGGVAM
     GMYNQDKSIE DFAHSSFQMA LSKGWPLYLS TKNTILKKYD GRFKDIFQEI YDKQYKSQFE
     ARKIWYEHRL IDDMVAQAMK SEGGFIWACK NYDGDVQSDS VAQGYGSLGM MTSVLVCPDG
     KTVEAEAAHG TVTRHYRMYQ KGQETSTNPI ASIFAWTRGL AHRAKLDNNK ELAFFANALE
     EVSVETIEAG FMTKDLAACI KGLPNVQRSD YLNTFEFMDK LGENLKIKLA QAKL
//